This work describes the organocatalytic alpha-trifluoromethylthiolation of silylenol ethers using N-(trifluoromethylthio)saccharin as trifluoromethylthiolating reagent that is activated by the presence of catalytic amounts of a Lewis base. Tetrahydrothiophene was identified as the best organocatalyst and it was successfully employed to promote the synthesis of different alpha-trifluoromethylketones; the reaction has been performed under a traditional batch methodology and under continuous flow conditions. In general, yields obtained using the traditional batch process were higher than those observed when the reaction was performed under flow conditions. However, short reaction times, higher productivity and higher space time yields were observed when a flow system process was employed. Preliminary DFT calculations were also performed in order to elucidate the mechanism of the reaction.

A new class of solid supported chiral imidazolidinone organocatalysts for the catalytic reduction of imines with trichlorosilane has been developed. Polystyrene proved to be a more effective support than silica in terms of both chemical and stereochemical efficiency. Even with a loading as low as 1 mol% the best performing supported catalyst showed a remarkable activity and stereocontrol ability, promoting the reduction with stereoselectivities reaching 98% ee and in most cases ranging between 90-95% ee The general scope of the methodology and the good recyclability of the immobilized catalyst were demonstrated. The polystyrene-anchored chiral catalyst was also used to prepare packed bed reactors for the continuous flow synthesis of chiral amines, that were obtained in excellent yields and enantioselectivities. By exploiting the chiral organocatalytic reactor, the in-flow stereoselective synthesis of a common, immediate precursor of rivastigmine, of the calciomimetic (R)-NPS 568 and of Acrylamide (S)-A, currently under study for the treatment of neuropathic pain, was successfully accomplished.

The formation of novel chiral bidentate phosphoroamides structures able to promote Lewis base-catalyzed Lewis acid-mediated reactions was investigated. Two different classes of phosphoroamides were synthetized: the first class presents a phthalic acid/primary diamine moiety, designed with the aim to perform a self-assembly recognition process through hydrogen bonds; the second one is characterized by the presence of two phosphoroamides as side arms connected to a central pyridine unit, able to chelate SiCl4 in a 2:1 adduct. These species were tested as organocatalysts in the stereoselective allylation of benzaldehyde and a few other aromatic aldehydes with allyl tributyltin in the presence of SiCl4 with good results. NMR studies confirm that only pyridine-based phosphoroamides effectively coordinate tetrachlorosilane and may lead to the generation of a self-assembled entity that would act as a promoter of the reaction. Although further work is necessary to clarify and confirm the formation of the hypothesized adduct, the study lays the foundation for the design and the synthesis of chiral supramolecular organocatalysts.

The mechanism of a recently reported, highly chemoselective metal-free protocol of wide general applicability for the reduction of aromatic and aliphatic nitro-derivatives to amines has been investigated. The reaction is supposed to occur through the generation of a Si(II) reducing species; quantum mechanical calculations, and spectroscopic and experimental data strongly suggest the tertiary amine-stabilized dichlorosilylene to be the most probable reducing agent.

The stereoselective direct aldol reaction of S-phenyl thioesters and aromatic aldehydes promoted by tetrachlorosilane was realized for the first time; the proposed mechanism involves the formation of a chiral cationic hypervalent silicon species and requires the presence of catalytic amounts of a Lewis base, like a chiral phosphine oxide. The reaction affords syn -hydroxy thioesters as major isomers in good yields, high diastereoselectivity (up to 99:1), and up to 92% enantiomeric excess. The absolute configuration of the major isomer was established by converting the product into the corresponding -hydroxy ester. The scope of the reaction was also investigated by employing differently substituted thioesters in combination with different aromatic aldehydes.

AbstractThe title reaction between aryl substituted thioesters and aryl or hetaryl esters provides the corresponding β‐hydroxy thioesters in moderate yield, with no to excellent diastereomeric and moderate to high enantioselectivity.

An efficient organocatalytic methodology has been developed to perform the stereoselective addition of 2-carboxythioesters-1,3-dithiane to nitroalkenes. Under mild reaction conditions γ-nitro-β-aryl-α-keto esters with up to 92% ee were obtained, realizing a formal catalytic stereoselective conjugate addition of the glyoxylate anion synthon. The reaction products are versatile starting materials for further synthetic transformations; for example, the simultaneous reduction of the nitro group and removal of the dithiane ring was accomplished, allowing the preparation of a GABAB receptor agonist baclofen.

AbstractThe enantioselective organocatalyzed conjugate addition of a newly activated thioester acting as an acyl anion mimic is presented using a chiral bifunctional catalyst to control the stereochemistry.

9-Amino-9-deoxy-epi-quinine, properly modified by suitable linkers, was anchored on highly cross-linked polystyrene, poly(ethylene glycol), and silica. The resulting species were characterized by NMR spectroscopy and tested as supported organocatalysts in the reaction between isobutyric aldehyde and trans--nitrostyrene. Polystyrene- and poly(ethylene glycol)-supported catalysts outperformed their nonsupported counterpart affording the desired product in high yield and ee (>90% ee). Silica-supported catalysts proved to be less efficient in terms of both chemical yield and enantioselectivity. Polystyrene- and poly(ethylene glycol)-supported 9-amino-9-deoxy-epi-quinine were then used in the same reaction with different substrates, leading to the desired products in high yield and ee, as well as in three other reactions operating with different mechanism. An investigation of the recyclability of the polystyrene- and poly(ethylene glycol)-supported systems showed that these could be recovered and recycled with no loss of stereochemical activity but with a marked erosion of chemical efficiency occurring at the fifth reaction cycle. This was ascribed to chemical degradation of the alkaloid occurring during the reaction.

The vapor-phase deposition of triethoxy(octyl)-silane and 1H,1H,2H,2H-perfluoroctyltriethoxysilane on silica substrates was studied at different temperatures (70-150 degrees C). An original combination of spectroscopic (C-13 and Si-29 solid state NMR, FTIR), electrochemical (CV, EIS), and surface (surface free energy determinations, AFM) characterization techniques was adopted to shed light on the role played by the alkylsilane structure and deposition temperature on the resulting layer. As for the unfluorinated molecule, both wettability and ion permeability displayed a bell-shaped curve with respect to the functionalization temperature. Spectroscopic techniques showed similar trends in the functionalization degree and suggested the formation of oligomers/polymers covalently attached to the surface. Si-29 NMR proved that higher functionalization temperatures increase lateral polymerization across the alkylsilane layer. Conversely, the wettability was almost invariant with functionalization temperature for the fluorinated analogue. However, electrochemical and spectroscopic results had a significant dependence on the functionalization conditions, even more marked than for the unfluorinated alkylsilane. The higher thermal reactivity of fluorinated molecules led to vertical polymerization, as supported by very high water contact angles, diffusion components in EIS, and a lower degree of covalent bonding with the surface. Optimal deposition conditions were identified at 100 and 90 degrees C for the unfluorinated and fluorinated alkylsilane, respectively.

A metal-free stereoselective catalytic addition of in situ generated dienamine to -nitroacrylates has been developed. Starting from simple ,-unsaturated ketones, highly functionalized chiral -nitrocyclohexanecarboxylic esters were obtained in a single step, in good yields and up to 98% ee. By an unprecedented mechanistic pathway, starting from the synthetically readily available E-nitroacrylate, the present methodology allowed us to obtain as major product the isomer bearing a cis relative disposition between the nitro and the ester groups, which is not accessible via a classical Diels-Alder reaction.

Starting from (E)-β-substituted-β-nitroacrylates and α,β-unsaturated ketones, a stereoselective organocatalyzed one-pot methodology allowed to synthesize highly decorated chiral 2-nitro-cyclohexane carboxylic esters. The reaction is promoted by Cinchona alkaloid-derived primary amines in the presence of an acidic co-catalyst and affords two diastereoisomers, in good yields and high enantiomeric excess (often higher than 90% ee). By replacing conventional heating with microwave irradiation, cleaner reactions in shortened times (from 48h to 30min) were obtained, with improved dr (80:20) and high ee (up to 94%). The application of microwave technology to this organocatalytic methodology allowed also employing C1 substituted enones, leading to cyclohexanones with four contiguous stereocenters in two isomers only, and up to 99% enantioselectivity.

Siloxane/oxide hybrids have attracted growing attention thanks to their ability to modulate the surface energy, wettability, or self-lubricity of a material. Here, we compare two functionalisation procedures (chemical vapour deposition and wet impregnation) on substrate films composed by preformed oxide particles. Three kinds of particles, characterised by different natures (SiO 2 and TiO 2 ) and average particle size, were studied to highlight possible effects related to the chemical and morphological state of the substrate surface. Morphological characterisations were carried out using dynamic light scattering and scanning electron microscopy, while the structure of the hydrophobing layer was studied by combining Fourier transform infrared spectroscopy and solid-state nuclear magnetic resonance. The degree of functionalisation and the features of the siloxane layer vary significantly among the adopted oxides and functionalisation methods. The wettability features of the different hybrids closely mirror the results of the spectroscopic characterisations, giving rise to either Lotus leaf or patch-wise hydrophobic systems depending on the adopted conditions.

AbstractThe chiral imidazolidinone (SMI) immobilized on mesoporous silica nanoparticles, efficiently promotes the asymmetric cycloaddition of unsaturated aldehydes to cyclopentadiene.

The synthesis of chiral imidazolidinones on mesoporous silica nanoparticles, exploiting two different anchoring sites and two different linkers, is reported. Catalysts 1-4 were prepared starting from l-phenylalanine or l-tyrosine methyl esters and supporting the imidazolidinone onto silica by grafting protocols or azide-alkyne copper(I)-catalyzed cycloaddition. The four catalysts were fully characterized by solid-state NMR, N2 physisorption, SEM, and TGA in order to provide structural assessments, including an evaluation of surface areas, pore dimensions, and catalyst loading. They were used in organocatalyzed Diels-Alder cycloadditions between cyclopentadiene and different aldehydes, affording results comparable to those obtained with the nonsupported catalyst (up to 91% yield and 92% ee in the model reaction between cyclopentadiene and cinnamic aldehyde). The catalysts were recovered from the reaction mixture by simple filtration or centrifugation. The most active catalyst was recycled two times with some loss of catalytic efficiency and a small erosion of ee.

Continuous-flow organocatalyzed Diels-Alder reactions have been performed with excellent enantioselectivity for the first time in a chiral "homemade" HPLC column, packed with silica on which a MacMillan catalyst has been supported by a straightforward immobilization procedure. The versatility of the system was also proven by running with the same column continuous-flow stereoselective reactions with three different substrates, showing that the catalytic reactor may efficiently work in continuo for more than 150 h; the regeneration of the HPLC column was also demonstrated, allowing to further extend the activity of the reactor to more than 300 operating hours.

Oxide-based hybrids are promising systems to modulate the surface properties and impart different functionalities. Here, the wettability features of rough titanium dioxide (TiO2) layers derivatized by siloxanes are tailored with respect to both water and nonaqueous solvents. The adopted synthetic procedure is very simple and may be extended to different substrates, as it is based on the direct functionalization of homemade, tailored, TiO2 nanoparticles by different siloxanes, both fluorinated and nonfluorinated. Nanotitania provides a multiscale roughness able to impart super-hydrophobicity and its photocatalytic activity can be exploited to obtain surfaces with patterned wettability by photocatalytic lithography. The behavior of the different siloxanes (oleophobicity degree, self-cleaning properties, and kinetics of ultraviolet degradation) is related to the surface energy components of the bare siloxane films, evaluated by Owens-Wendt classical model, and to the structure of the siloxane monolayer at the TiO2 surface, as determined by C-13 and Si-29 solid-state nuclear magnetic resonance. Finally, patterned structures with tunable hydrophobic and oleophobic patches are obtained by using the photocatalytic activity of the oxide. The siloxane photodegradation process is analyzed by Fourier transform infrared spectroscopy. The resulting wetting contrast is exploited to obtain a site selective adsorption of a dye molecule. The presented procedure can be applied to obtain the site selective deposition or growth of a large variety of materials, such as semiconductor quantum dots, polymers, or biological molecules.

Takemoto promotes: Enantiomerically pure bifunctional chiral catalysts are immobilized on poly(methylhydrosiloxane). A supported Takemoto-type catalyst promoted the diethyl malonate addition to nitrostyrene in fair to good yields and up to 83 % ee, and its recyclability is demonstrated. Detailed facts of importance to specialist readers are published as "Supporting Information". Such documents are peer-reviewed, but not copy-edited or typeset. They are made available as submitted by the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.